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Serotonin decreases HIV‐1 replication in primary cultures of human macrophages through 5‐HT 1A receptors
Author(s) -
Manéglier B,
Guillemin G J,
Clayette P,
RogezKreuz C,
Brew B J,
Dormont D,
Advenier C,
Therond P,
SpreuxVaroquaux O
Publication year - 2008
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/bjp.2008.80
Subject(s) - receptor , flow cytometry , biology , serotonin , in vitro , macrophage , cell culture , receptor expression , microbiology and biotechnology , viral replication , 5 ht receptor , virus , immunology , biochemistry , genetics
Background and purpose: 5‐HT (serotonin) is known to be involved in neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV) targets cells such as monocytes/macrophages, which colocalize with 5‐HT‐releasing cell types, mostly platelets. In this study, we investigated the effects of 5‐HT on HIV‐1‐infected macrophages in vitro . Experimental approach: Human macrophages cultured in serum‐free medium were treated over 7 days with 5‐HT at three concentrations (0.01, 1 and 100 μ M ) with or without agonists and antagonists of 5‐HT 1A and 5‐HT 2 receptors. After 7 days of treatment, macrophages were infected with HIV‐1/Ba‐L and virus replication was monitored over 16 days and expression of proviral HIV DNA was investigated by PCR after 24 h of infection. Cell surface expression of HIV‐1/Ba‐L receptor (CD4) and coreceptor (CCR5) was investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein‐1α (MIP‐1α), was quantified by ELISA in cell culture supernatants and MIP‐1α mRNA expression was assessed by reverse transcriptase‐PCR. Key results: In vitro , 5‐HT downregulated the membranous expression of CCR5 and led to a decrease of HIV‐1 infection, probably through its action on 5‐HT 1A receptors. 5‐HT (100 μ M ) was also able to induce overexpression of MIP‐1α mRNA leading to an increase of MIP‐1α secretion by human macrophages. Conclusions and implications: The effects of 5‐HT on HIV infection could be a consequence of the increase in MIP‐1α concentrations and/or CCR5 receptor downregulation. These results suggest that 5‐HT can inhibit the replication of HIV‐1 in primary culture of human macrophages through its action on 5‐HT 1A receptors.